Jan 13, 2020

EDITOR’S CHOICE IN CELL BIOLOGY

Female of most mammalian species are fertile throughout their adult life. But humans are different, says University of Copenhagen molecular geneticist Eva Hoffmann. A woman’s fertility follows a curve, increasing from puberty, peaking in her 20s, and falling rapidly starting in her mid-30s.

Researchers attribute this decline partly to a rise in egg aneuploidy, or incorrect chromosome number, which can lead to pregnancy failure. Hoffmann and colleagues wanted to know more about how aneuploidy occurs in human eggs, and whether it’s connected to female fertility from a young age.

The team collected more than 3,000 eggs from women between 9 and 43 years old through a collaboration with IVF clinics and Danish hospitals that preserve ovarian tissue from cancer patients about to undergo chemotherapy. The researchers found, as expected, that older women’s eggs showed higher-than-normal rates of aneuploidy. Surprisingly, eggs from young girls showed high rates too, resulting in a U-shape aneuploidy curve—the inverse of the relationship between fertility and age.

This egg aneuploidy has to do with the molecular glue that holds sister chromatids together, Hoffmann says. In older women, the team showed, the glue fails prematurely during cell division; in girls, it’s over-effective, releasing chromatids later than usual. Both abnormalities can influence chromatid segregation and result in aneuploidy.

The study is “Herculean in its efforts,” says Karen Schindler, a reproductive biologist at Rutgers University who was not involved in the work. Using girls’ eggs was a “unique and important approach” that “really fleshes out [what’s happening at] the younger age.” However, she notes, there could be other mechanisms behind age-related changes in aneuploidy rates.

The findings have implications for researchers’ understanding and treatment of infertility, not just in older women but in young girls who freeze their eggs for health reasons, Schindler adds. A girl’s eggs “clearly behave differently than they do when she’s reproductive age.”